Method for preparing 1,3,5-triaminobenzene and hydrolyzing it into high-purity phloroglucinal

ABSTRACT

The invention concerns a method for method for preparing 1,3,5-triaminobenzene, characterized in that it comprises a step which consists in amination of a compound of formula (I), wherein: A represents a halogen atom or a NH 2  group; X 1  and X 2 , identical or different, represent each a halogen atom, the amination step being carried out in the presence of ammonia and a catalyst selected from the group consisting of copper salts, cupric and cuprous oxides or mixtures thereof at a temperature ranging between 150° C. and 250° C. and at a pressure higher that 35 bars

The present invention relates to a method of preparing1,3,5-triaminobenzene and its hydrolysis and subsequent purification tohigh-purity phloroglucinol.

Phloroglucinol is a compound known both to the colorist and to thepharmacist. Phloroglucinol initially attracted interest for its use indyeing for papers or textiles. It was only later that pharmacistsuncovered its musculotropic antispasmolytic properties. It is clear,however, that the purity requirements are much higher whenphloroglucinol is used as an antispasmodic than as a dyeing agent.

The literature extensively describes the preparation of phloroglucinolby hydrolysis of 1,3,5-triaminobenzene in the presence of concentratedhydrochloric acid. 1,3,5-Triaminobenzene therefore represents a verywidely used intermediate in the preparation of phloroglucinol.

As far as the preparation of 1,3,5-triaminobenzene is concerned, a largenumber of synthesis routes have already been proposed.

Among the synthesis routes already proposed, mention may be made of U.S.Pat. No. 4,380,670. That patent describes the preparation of1,3,5-triaminobenzene from 3,5-diaminochlorobenzene in the presence ofammonia and of salts or oxides of copper in various oxidation states ata temperature of between 150 and 250° C. That patent specifies,moreover, in column 1, lines 38 to 42, that the preparation of1,3,5-triaminobenzene by direct amination of 1,3,5-trichlorobenzene isnot possible. The authors of the patent clearly indicate that thedesired amination reaction does not take place.

Another possible synthesis route for 1,3,5-triaminobenzene is describedby H. T. Clarke and W. W. Hartman in the article entitled“Phloroglucinol”, organic synthesis, vol. 45. In that article,1,3,5-triaminobenzene is obtained starting from 2,4,6-trinitrobenzoicacid in concentrated hydrochloric acid in the presence of tin. However,the synthesis of trinitrobenzoic acid is relatively lengthy and awkward,necessitating the preparation of trinitrotoluene (TNT), which isexplosive. Moreover, the preparation of 1,3,5-triaminobenzene startingfrom trinitrobenzoic acid gives rise to difficulties of purification.This is because, following hydrolysis of 1,3,5-triaminobenzene, it isparticularly difficult to purify the resulting phloroglucinol.Consequently, a high-purity phloroglucinol meeting pharmaceuticalrequirements cannot be obtained by that route.

As regards, more specifically, the subsequent step of hydrolysis of1,3,5-triaminobenzene to give phloroglucinol, mention may be made ofU.S. Pat. No. 4,115,451. That patent recommends hydrolysis of1,3,5-triaminobenzene in an excess of concentrated hydrochloric acid ata temperature of 100 to 200° C., to end up with phloroglucinol. Thishydrolysis step is followed by a step of extraction with an aceticester. The extracted phase containing the phloroglucinol crystallizesafter cooling. After filtration, the phloroglucinol is recrystallizedfrom water containing active carbon.

In spite of all this literature relating to the synthesis of1,3,5-triaminobenzene and relating to the hydrolysis to phloroglucinol,the preparation of a high-purity phloroglucinol still poses numerousproblems to the industrialists of the pharmaceutical sector. The purityrequirements imposed by the pharmacopeia call for a method of synthesiswhich yields a phloroglucinol which is in accordance with the criteriaof pharmaceutical purity.

On the other hand, improving the synthesis routes, in particular thecost price of the raw materials, and reducing the number of synthesissteps have favorable consequences for the manufacturing costs of apharmaceutical active principle.

It is while working in this direction that the inventors have succeededin developing a method of preparing 1,3,5-triaminobenzene and thenhydrolyzing it to phloroglucinol, which is original, effective and lesscostly. This method also makes it possible to obtain a high-purityphloroglucinol which is entirely in accordance with pharmaceuticalrequirements.

In general, the invention provides a method of preparing1,3,5-triaminobenzene which comprises a step a) of amination of acompound of formula (I):

in which:

-   -   A represents a halogen atom or an NH₂ group,    -   X₁ and X₂, which are identical or different, each represent a        halogen atom,        said amination step being conducted in the presence of ammonia        and a catalyst selected from the group consisting of copper        salts, cupric and cuprous oxides and mixtures thereof, at a        temperature ranging from 150° C. to 250° C. and at a pressure of        greater than 35 bars.

It should be noted that the method according to the invention isentirely original in relation to the prior art presented above.

This is because, as described earlier on above, the inventors have goneagainst a technical prejudice from the U.S. Pat. No. 4,380,670 and haveovercome it. The inventors have discovered, against all expectation,that it is possible to carry out the amination of the compound offormula (I), that is, in particular, of 1,3,5-triaminobenzene or of3,5-dichloroaniline, and to obtain 1,3,5-triaminobenzene quantitatively,in a single step, and starting from compounds which are stable andavailable commercially.

In formula (I) A represents an NH₂ group or a halogen atom, i.e.,bromine, chlorine, fluorine or else iodine. Preferably A represents anNH₂ group, bromine or chlorine, and more preferably chlorine.

X₁ and X₂ are identical or different from one another and represent ahalogen atom, i.e., as indicated above, bromine, chlorine, fluorine orelse iodine, preferably chlorine or bromine.

Advantageously X₁ and X₂ are identical and each represent a bromine orchlorine atom, preferably a chlorine atom.

The preferred compounds (I) are 1,3,5-triaminobenzene,3,5-dichloroaniline, 1,3,5-tribromobenzene or 3,5-dibromoaniline.

As far as the catalyst is concerned it is preferably selected from thegroup consisting of halogen salts of copper, also called copper halides,and more preferably from copper bromide, copper chloride, copper iodideand mixtures thereof.

This catalyst is preferably used in amounts ranging from 1% to 5%, thispercentage expressing the total weight of catalyst, based on the totalweight of reactant.

Moreover, this step a) is conducted in the presence of an ammoniasolution whose concentration is preferably from 20% to 30%, and morepreferably whose concentration is 28%.

In the process according to the invention, this ammonia solution is usedin an amount ranging preferably from 70% to 95% by weight, based on thetotal weight of the reactants.

The process according to the invention may further comprise anadditional step of hydrolysis of the 1,3,5-triaminobenzene tophloroglucinol, and also possible steps of purification of the lattercompound.

The process according to the invention provides, moreover, a1,3,5-triaminobenzene which is particularly appropriate for use forpreparing phloroglucinol by hydrolysis.

This hydrolysis may thus be carried out as follows:

-   -   b) hydrolysis of the 1,3,5-triaminobenzene obtained in step a)        in the presence of hydrochloric acid or of sulfuric acid at a        temperature greater than 90° C., and preferably from 100 to 120°        C., for a time of 6 to 24 h, to give a hydrolysate containing        phloroglucinol,    -   c) optionally filtration at ambient temperature of the        hydrolysate obtained in step b),    -   d) extraction of phloroglucinol from the hydrolysate obtained in        step b) or from the filtrate obtained in step c), using ethyl        ether or another, ester-based solvent, for example, ethyl        benzoate, ethyl acetate, isopropyl acetate or n-butyl acetate.

In this hydrolysis step the hydrochloric acid may in particular be at aconcentration of 20% to 40%, preferably a concentration of 37%, and inamounts ranging from 10% to 15% by weight, based on the total weight ofreactant. The sulfuric acid may be at a concentration of 10% V to 100%V, preferably from 50% V to 98% V, the amounts ranging from 2 to 6 H⁺equivalents, preferably 4 H⁺ equivalents.

It is possible to follow a number of routes for the purification of thephloroglucinol.

One of these routes comprises the following step:

-   -   e1) recrystallization of the phloroglucinol obtained in step d)        from water containing active carbon, to give a high-purity        phloroglucinol.

Another route comprises the succession of the following steps:

-   -   e2) concentration of the hydrolysate obtained in step b) or of        the phloroglucinol solution obtained in step d) until        phloroglucinol precipitates,    -   f2) filtration of the precipitate obtained in step e2),    -   g2) recrystallization of the phloroglucinol obtained in step f2)        from water containing active carbon,    -   h2) takeup of the recrystallized phloroglucinol obtained in step        g2) in ethyl ether containing active carbon, to give a        phloroglucinol solution,    -   i2) evaporation of the phloroglucinol solution obtained in step        h2), to give a high-purity phloroglucinol.

In these purification steps, both the active carbon and the solvents areused in amounts which are commonly employed by the skilled worker.

This purification method involves the use of ether and makes it possibleto isolate a phloroglucinol which meets the requirements of thepharmacopeia, since it exhibits, among other properties, a colorationless than or equal to BY 5.

Purity control analyses were carried out according to methods describedin the present patent application. According to these analyses thephloroglucinol obtained according to the method of the inventioncontains, in total, less than 0.5% of impurities, preferably less than0.2% of impurities and more preferably still less than 0.1% ofimpurities by weight, based on the total weight of phloroglucinolobtained.

The three impurities which are most characteristic and most widelyrepresented in this type of phloroglucinol preparation are3,5-dichloroaniline, phloroglucide and resorcinol. Measurement has shownthat the phloroglucinol obtained according to the method of theinvention contains not more than 0.1%, preferably not more than 0.05%and more preferably not more than 0.01% of these three impurities byweight, based on the total weight of phloroglucinol obtained.

Impurity levels of this kind completely satisfy the requirements calledfor by the French pharmacopeia. Consequently the phloroglucinol obtainedby the method according to the invention is entirely indicated for thepreparation of a medicinal product, in particular for the treatment ofdisorders associated with muscular spasms or for the treatment of painin a mammal.

METHODS USED FOR THE ANALYSES

A—Identification

The phloroglucinol obtained is checked according to the monograph“Phloroglucinol” in the French Pharmacopeia, Xth edition, July 1987.

Infrared spectrum: 3211 cm⁻¹, 1624 cm⁻¹, 1506 cm⁻¹, 1419.5 cm⁻¹, 1157.2cm⁻¹, 1008.7 cm⁻¹, 813 cm⁻¹

¹H NMR spectrum at 300 MHz in DMSOd6: 5.8 ppm (s, 3H, C—H) and 9.1 ppm(s, 3H, O—H).

¹³C NMR spectrum at 300 MHz in DMSOd6: 95.9 (C—H); 159.6 (C—OH).

B—Purity

The impurities looked for are primarily 3,5-dichloroaniline,phloroglucide, which results from the dimerization of phloroglucinol,and resorcinol.

3,5-Dichloroaniline is present in the phloroglucinol produced when themethod according to the invention proceeds via step a).3,5-Dichloroaniline is in effect one of the reactants of this step. Incontrast, phloroglucide and resorcinol are present in phloroglucinolirrespective of its preparation steps.

In practice, high-performance liquid chromatography is used in order tolook for these impurities. The methods which can be used are inparticular as follows:

1—Identification and Assay of 3,5-dichloroaniline

1.a—Comparative High-performance Liquid Chromatography:

Preparation of Solutions:

Eluent: acetonitrile —H₃PO₄ (85%) at 0.5 g.l⁻¹ of water;

-   -   Control solution (T₁): dissolve 20.0 mg of reference        3,5-dichloroaniline in 100 ml of eluent (96% alcohol;        acetonitrile, dilute acid);    -   Type of column: Agilent Interchim ZORBAX SB-CN column        (4.6×250 mm) 5 μm, held at 35° C. with detection at 220 nm and a        flow rate of 1 ml.min⁻¹;    -   Control solution (T₂): dilute control solution (T₁) to 1/100th        in water;    -   Assay solution (E): dissolve 200.0 mg of phloroglucinol to be        analyzed in 100 ml of water.        Technique:

The techniques employed may vary slightly depending on the equipmentused. By way of example the technique may be as follows:

-   -   inject exactly 10 μl of each of the control solutions and assay        solution into a suitably equipped and regulated chromatograph.    -   for each of the solutions measure the areas of the peaks        obtained and their attention time. 3,5-Dichloroaniline gives a        peak having a retention time RT=6.4 min.        Calculation:        Let:

-   A₁ be the value of the area of the 3,5-dichloroaniline peak obtained    for control solution (T2);

-   A₂ be the value of the area of the 3,5-dichloroaniline peak obtained    for the assay solution (E).

The % of 3,5-dichloroaniline content will be given by the expression:t=(A ₂ /A ₁)×0.1Expression of the Result:

The 3,5-dichloroaniline content of the phloroglucinol must not begreater than 0.1%.

2—Identification and Assay of Phloroglucide

2.a—Comparative High-performance Liquid Chromatography:

-   -   column: Agilent Interchim ZORBAX SB-CN (4.6×250 mm) 5 μm, held        at 35° C.;    -   1.5 ml.min⁻¹—detection: 220 nm.        Preparation of Solutions:    -   Eluent: H₃PO₄ (85%) at 0.5 g.l⁻¹ of water;    -   Control solution (T₁): dissolve 20.0 mg of reference        phloroglucide in 100 ml of methanol;    -   Control solution (T₂): dilute control solution (T₁) to 1/100th        in water;    -   Assay solution (E): dissolve 200 mg of phloroglucinol to be        analyzed in 100 ml of water.        Technique:

The techniques employed may vary slightly according to the equipmentused. By way of example the technique may be as follows:

-   -   inject exactly 10 μl of each of the control solutions and assay        solution into a suitably equipped and regulated chromatograph.    -   for each of the solutions measure the areas of the peaks        obtained and their retention time. Phloroglucide gives a peak        having a retention time of T_(R)=12.6 min and resorcinol a        chromatographic peak of T_(R)≈7.0 min.        Calculation:        Let:

-   A₁ be the value of the area of the peak of impurity obtained for the    control solution;

-   A₂ be the value of the area of the peak of impurity obtained for the    assay solution.

The % phloroglucide content will be given by the expression:t=(A ₂ /A ₁)×0.1Expression of the Result:

The phloroglucide content of the phloroglucinol must not be greater than0.1%.

The invention will now be described in greater detail by means of theexamples which follow. The purpose of these examples is to illustratethe method of the invention without limiting it to these simpleembodiments.

EXAMPLE 1 Preparation of 1,3,5-triaminobenzene from1,3,5-trichlorobenzene and its hydrolysis to phloroglucinol

A pressurized vessel is charged with 5 g (27.5 mmol) of1,3,5-trichlorobenzene and 70 ml of 28% aqueous ammonia and 800 mg ofcopper iodide are added. The mixture is heated at 180° C. and at apressure of 40 bar for 24 h. After the mixture has cooled, 40 g ofcrushed ice and 79 ml of concentrated hydrochloric acid are added andthen the mixture is heated at 120° C. for 20 h. The contents of theflask are filtered. The filtrate is subsequently extracted with 3×40 mlof ethyl ether. The ethereal phase is subsequently dried and thenevaporated to give 1.4 g of phloroglucinol, corresponding to a yield of40%

EXAMPLE 2 Preparation of 1,3,5-triaminobenzene from 3,5-dichloroanilineand its hydrolysis to phloroglucinol

A pressurized vessel is charged with 3 g (18.5 mmol) of3,5-dichloroaniline and 50 ml of 28% aqueous ammonia and 300 mg ofcopper iodide are added. The mixture is heated at 180° C. and at apressure of 40 bar for 24 h. After the mixture has been cooled, 30 g ofcrushed ice and a concentrated, 37% solution of hydrochloric acid areadded to a pH of 1, and then the mixture is heated at 120° C. for 20 h.

The contents of the flask are filtered. The filtrate is subsequentlyextracted with 3×40 ml of ethyl ether, dried and then evaporated. Thisgives a phloroglucinol yield of the order of 60%.

EXAMPLE 3 Hydrolysis of 1,3,5-triaminobenzene to phloroglucinol and itsextraction with ethyl ether

2.2 g (18 mmol) of 1,3,5-triaminobenzene in 150 ml of a 2 N aqueoussolution of hydrochloric acid are heated at 100° C. for 18 h. Aftercooling to ambient temperature, the solution is filtered. The aqueousphase is subsequently extracted with 3×40 ml of ethyl ether. Theethereal phases are dried over sodium sulfate, filtered and thenevaporated.

The phloroglucinol obtained is subsequently recrystallized from 17 ml ofwater containing 15 mg of active carbon, giving 1.5 g of purephloroglucinol.

EXAMPLE 4 Hydrolysis of 1,3,5-triaminobenzene to phloroglucinol and itspurification with ethyl ether

5 g of 1,3,5-triaminobenzene in 300 ml of a 0.5 N aqueous solution ofhydrochloric acid are heated at 120° C. for 15 hours. After cooling, thesolution is concentrated until the phloroglucinol precipitates. Thefiltered precipitate is recrystallized from 40 ml of water with activecarbon. The product obtained is subsequently taken up in a minimum ofethyl ether and heated for 15 minutes with active carbon. Evaporationgives 2.9 g of pure product.

EXAMPLE 5 Preparation of 1,3,5-triaminobenzene from 3,5-dichloroaniline,hydrolysis with hydrochloric acid of the 1,3,5-triaminobenzene tophloroglucinol.

A pressurized vessel is charged with 30 g (18.6 mmol) of3.5-dichloroaniline and 1.8 g of copper iodide in 160 ml of 28% aqueousammonia. The mixture is heated at 190° C. and under a pressure of 40bars for 24 h. The contents of the vessel are poured into 200 ml ofwater and then the excess ammonia is removed. Then 56 g of 10 Nhydrochloric acid are added and the mixture is heated at 110° C. for 20h. Following filtration, the solution is cooled in an ice bath until thephloroglucinol precipitates. The precipitate obtained is subsequentlyrecrystallized from 400 ml of a water-methanol (95 V–5 V) mixture. Asecond recrystallization from the same mixture gives 12.5 g of purephloroglucinol.

EXAMPLE 6 Preparation of 1,3,5-triaminobenzene from 3,5-dichloroaniline;hydrolysis with sulfuric acid of the 1,3,5-triaminobenzene tophloroglucinol, and purification

A pressurized vessel is charged with 30 g (18.6 mmol) of3,5-dichloroaniline and 1.5 g of copper chloride in 160 ml of 28%aqueous ammonia. The mixture is heated at 190° C. and under a pressureof 37 bars for 24 hours. The contents of the vessel are poured into 200ml of water and then the excess ammonia is removed. Then 37 g of 98%sulfuric acid are added and the mixture is heated at 110° C. for 20hours. Following filtration, the solution is concentrated to a third andthen cooled in an ice bath until the phloroglucinol precipitates. Theprecipitate obtained is subsequently recrystallized from 350 ml of awater-ethanol (93 V–7 V) mixture. A second recrystallization from watergives 13 g of pure phloroglucinol.

1. A method of preparing 1,3,5-triaminobenzene, comprising a step a) ofamination of a compound of formula (I):

in which: A represents a halogen atom or an NH2 group, X1 and X2, whichare identical or different, each represent a halogen atom, saidamination step being conducted in the presence of ammonia and a catalystselected from the group consisting of copper salts, cupric and cuprousoxides and mixtures thereof, at a temperature ranging from 150° C. to250° C. and at a pressure of greater than 35 bar.
 2. The method of claim1, wherein A represents a bromine atom, a chlorine atom or NH2 group. 3.The method of claim 1, wherein X1 and X2 are identical and eachrepresent a chlorine atom or a bromine atom.
 4. The method of claim 1,wherein the catalyst is selected from the group consisting of copperhalides and cupric and cuprous oxides.
 5. The method of claim 1, whereinthe aqueous ammonia possesses a concentration of 20% to 30%.
 6. Themethod of claim 1, further comprising the steps of: b) hydrolysis of the1,3,5-triaminobenzene obtained at the end of the amination step in thepresence of hydrochloric acid or of sulfuric acid at a temperaturegreater than 90° C., for a time of 6 to 24 h, to give a hydrolysatecontaining phloroglucinol, c) optionally filtration at ambienttemperature of the hydrolysate obtained in step b), d) extraction ofphloroglucinol from the hydrolysate obtained in step b) or from thefiltrate obtained in step c), using ethyl ether or an ester-basedsolvent.
 7. The method of claim 1, further comprising the steps of: b)hydrolysis of the 1,3,5-triaminobenzene obtained at the end of theamination step at a temperature greater than 90° C., for a time of 6 to24 h, to give a hydrolysate containing phloroglucinol, wherein thehydrolysis is conducted in the presence of hydrochloric acid at aconcentration of 20% to 40% c) optionally filtration at ambienttemperature of the hydrolysate obtained in step b), d) extraction ofphloroglucinol from the hydrolysate obtained in step b) or from thefiltrate obtained in step c), using ethyl ether or an ester-basedsolvent.
 8. The method of claim 1, further comprising the steps of: b)hydrolysis of the 1,3,5-triaminobenzene obtained at the end of theamination step at a temperature greater than 90° C., for a time of 6 to24 h, to give a hydrolysate containing phloroglucinol, wherein thehydrolysis is conducted in the presence of sulfuric acid at aconcentration of 10% V to 100% V, c) optionally filtration at ambienttemperature of the hydrolysate obtained in step b), d) extraction ofphloroglucinol from the hydrolysate obtained in step b) or from thefiltrate obtained in step c), using ethyl ether or an ester-basedsolvent.
 9. The method of claim 1, further comprising the steps of: b)hydrolysis of the 1,3,5-triaminobenzene obtained at the end of theamination step in the presence of hydrochloric acid or of sulfuric acidat a temperature greater than 90° C., for a time of 6 to 24 h, to give ahydrolysate containing phloroglucinol, c) optionally filtration atambient temperature of the hydrolysate obtained in step b), d)extraction of phloroglucinol from the hydrolysate obtained in step b) orfrom the filtrate obtained in step c), using ethyl ether or anester-based solvent, e1) recrystallization of the phloroglucinolobtained in step c) or step d) from water containing active carbon, togive a high-purity phloroglucinol.
 10. The method of claim 1, furthercomprising the steps of: b) hydrolysis of the 1,3,5-triaminobenzeneobtained at the end of the amination step in the presence ofhydrochloric acid or of sulfuric acid at a temperature greater than 90°C., for a time of 6 to 24 h, to give a hydrolysate containingphloroglucinol, c) optionally filtration at ambient temperature of thehydrolysate obtained in step b), d) extraction of phloroglucinol fromthe hydrolysate obtained in step b) or from the filtrate obtained instep c), using ethyl ether or an ester-based solvent, e2) concentrationof the hydrolysate obtained in step c) or of the phloroglucinol solutionobtained in step d) until phloroglucinol precipitates, f2) filtration ofthe precipitate obtained in step e2), g2) recrystallization of thephloroglucinol obtained in step f2) from water containing active carbon,h2) takeup of the recrystallized phloroglucinol obtained in step g2) inethyl ether containing active carbon, to give a phloroglucinol solution,i2) evaporation of the phloroglucinol solution obtained in step h2), togive a high-purity phloroglucinol.
 11. The method of claim 1 furthercomprising the step of using the 1,3,5-triamiobenzene to producephloroglucinol.
 12. The method of claim 2 wherein A represents achlorine atom or a NH₂ group.
 13. The method of claim 12 wherein Arepresents a chlorine atom.
 14. The method of claim 3 wherein X₁ and X₂are identical and each represent a chlorine atom.
 15. The method ofclaim 4 wherein said catalyst is copper iodide.
 16. The method of claim5 wherein the aqueous ammonia possesses a concentration of 28%.
 17. Themethod of claim 6 wherein the hydrolysis of the 1,3,5-triaminobenzene instep b) is at a temperature of from 100 to 120° C.
 18. The method ofclaim 6 wherein the extraction of phloroglucinol from the hydrolysateobtained in step b) or from the filtrate obtained in step c) uses ethylbenzoate, ethyl acetate, isopropyl acetate or n-butyl acetate.
 19. Themethod of claim 7 wherein the hydrolysis of the 1,3,5-triaminobenzene instep b) is at a temperature of from 100 to 120° C.
 20. The method ofclaim 7 wherein the hydrolysis is conducted in the presence ofhydrochloric acid at a concentration of 37%.
 21. The method of claim 7wherein the extraction of phloroglucinol from the hydrolysate obtainedin step b) or from the filtrate obtained in step c) uses ethyl benzoate,ethyl acetate, isopropyl acetate or n-butyl acetate.
 22. The method ofclaim 8 wherein the hydrolysis of the 1,3,5-triaminobenzene in step b)is at a temperature of from 100 to 120° C.
 23. The method of claim 8wherein the hydrolysis of the 1,3,5-triaminobenzene is conducted in thepresence of sulfuric acid at the concentration of from 50% V to 98% V.24. The method of claim 8 wherein the extraction of phloroglucinol fromthe hydrolysate obtained in step b) or from the filtrate obtained instep c) uses ethyl benzoate, ethyl acetate, isopropyl acetate or n-butylacetate.
 25. The method of claim 9 wherein the hydrolysis of the1,3,5-triaminobenzene in step b) is at a temperature of from 100 to 120°C.
 26. The method of claim 9 wherein the extraction of phloroglucinolfrom the hydrolysate obtained in step b) or from the filtrate obtainedin step c) uses ethyl benzoate, ethyl acetate, isopropyl acetate orn-butyl acetate.
 27. The method of claim 10 wherein the hydrolysis ofthe 1,3,5-triaminobenzene in step b) is at a temperature of from 100 to120° C.
 28. The method of claim 10 wherein the extraction ofphloroglucinol from the hydrolysate obtained in step b) or from thefiltrate obtained in step c) uses ethyl benzoate, ethyl acetate,isopropyl acetate or n-butyl acetate.